Vascular diseases of the kidney

Vascular diseases of the kidney comprise a heterogeneous group of large-, medium-, and small-vessel disorders that impair renal blood flow, leading characteristically to hypertension, reduced glomerular filtration, and, in a subset of patients, progressive renal insufficiency and end-stage renal disease.

Introduction

A wide spectrum of local and systemic processes can involve the renal vascular tree, ranging from atherosclerotic narrowing of the main renal arteries to immune-mediated small-vessel vasculitis and thrombotic microangiopathies. Despite diverse etiologies, these entities share the common pathophysiologic hallmark of variable degrees of vessel obstruction with downstream ischemia, which provokes compensatory elevations in systemic blood pressure and reductions in glomerular filtration rate. Clinically, the dual presentation of hypertension and renal insufficiency often serves as an important clue to underlying renal vascular disease and underscores the need for timely diagnosis to prevent irreversible parenchymal injury and ESRD.

Large-vessel renal disease

Large-vessel disease predominantly affects the main renal arteries, their proximal branches, and the renal veins, and includes atherosclerotic renal artery stenosis, fibromuscular dysplasia, Takayasu arteritis, and renal vein thrombosis. Atherosclerotic renal artery stenosis (RAS) accounts for over 90% of cases of RAS and is typically defined angiographically by at least 50% luminal narrowing, most often involving the ostium and proximal third of the main renal artery or the perirenal aorta in older patients with generalized atherosclerosis. Fibromuscular dysplasia, a noninflammatory, non‑atherosclerotic arteriopathy, represents about 10% of RAS cases and shows characteristic angiographic subtypes—most commonly medial fibroplasia with a beads‑on‑a‑string pattern in the distal two thirds of the renal artery—predominantly in younger women.

Pathophysiologically, RAS leads to activation of the renin–angiotensin system in the ischemic kidney, reproducing the classic one‑clip Goldblatt model of renovascular hypertension, while chronic ischemia in the setting of atherosclerotic RAS may culminate in ischemic nephropathy. Diagnostic work‑up integrates clinical clues (abrupt or refractory hypertension, abdominal bruits, flash pulmonary edema, ACE inhibitor–induced azotemia) with noninvasive imaging: renal ultrasound for kidney size asymmetry, isotope renography (including captopril renogram), gadolinium‑enhanced MRA, and selective renal arteriography as the gold standard reserved for patients with positive screening tests. Management of atherosclerotic RAS remains controversial, as randomized and observational data suggest that percutaneous angioplasty—with or without stenting—and surgical revascularization seldom improve renal function and cure hypertension in fewer than one fifth of patients, making optimized pharmacologic blood pressure control the preferred strategy for most.

Takayasu arteritis is an inflammatory panarteritis of the aorta and its major branches that may secondarily involve the renal arteries, typically in young women with diminished pulses, limb claudication, and multiple bruits, fulfilling American College of Rheumatology criteria when at least three of six clinical and angiographic features are present. Therapy combines aggressive blood pressure control with corticosteroids as first‑line immunosuppression, methotrexate or other cytotoxic agents for steroid‑refractory disease, and surgical bypass of critical stenoses during quiescent phases; five‑year survival ranges from 80–90% overall but falls in patients with extensive arterial involvement. Renal vein thrombosis, most commonly seen in nephrotic syndrome (particularly membranous nephropathy), presents with acute flank pain and gross hematuria, is diagnosed by CT or MR venography, and is treated with long‑term warfarin anticoagulation, with generally favorable renal prognosis.

Medium‑sized vessel disease

Medium‑sized renal vessel disease is relatively rare and typically reflects systemic vasculitides such as polyarteritis nodosa (PAN) and Kawasaki disease. PAN is a necrotizing vasculitis of small muscular arteries with sparing of arterioles, capillaries, and venules, and absence of primary glomerular disease, often presenting with prolonged constitutional symptoms, livedo reticularis, dermal nodules, digital ischemia, and hypertension due to renal involvement. Histology shows pleomorphic inflammatory infiltrates in the adventitia, leukocytoclasis with transmural necrosis, and aneurysm formation; diagnosis relies on demonstrating these lesions by tissue biopsy or arteriography, as serology is nonspecific.

Approximately half of idiopathic PAN patients achieve remission with high‑dose prednisone, while cyclophosphamide is reserved for those with poor prognostic features captured in the five‑factor score (gastrointestinal involvement, renal insufficiency, proteinuria, CNS disease, cardiac manifestations). Kawasaki disease, another medium‑vessel vasculitis, rarely causes frank renal vasculitic lesions; renal manifestations more commonly include sterile pyuria, interstitial nephritis, or proteinuria, and are managed in the broader context of KD treatment.

Small‑vessel disease and glomerulopathy

Small‑vessel renal disease encompasses arterioles, capillaries, and venules and is closely linked to glomerular pathology, with many entities presenting as rapidly progressive glomerulonephritis (RPGN). ANCA‑associated vasculitides—Wegener granulomatosis, microscopic polyangiitis, and Churg–Strauss disease—are the most frequent small‑vessel vasculitides in adults and typically cause pauci‑immune necrotizing and crescentic glomerulonephritis accompanied by systemic features such as fever, purpura, arthralgias, neuropathy, and pulmonary involvement. Diagnosis is supported by high‑titer PR3‑ANCA in Wegener granulomatosis and MPO‑ANCA in microscopic polyangiitis in approximately 80% of cases, while 10% remain seronegative despite classic clinical and histologic findings.

Anti–glomerular basement membrane (anti‑GBM) disease accounts for about 20% of RPGN and is characterized by circulating IgG against the NC1 domain of the α3 chain of type IV collagen, linear IgG deposition along the GBM, and frequent pulmonary involvement in younger men, constituting the Goodpasture syndrome. Immune‑complex RPGN includes aggressive forms of IgA nephropathy, lupus nephritis (WHO classes III and IV), membranoproliferative glomerulonephritis, and postinfectious glomerulonephritis, all showing heavy immune‑complex deposition and often hypocomplementemia. Henoch–Schönlein purpura is a systemic IgA‑dominant vasculitis of venules and capillaries with a classic tetrad of purpura, arthralgias, abdominal pain, and renal involvement; most patients, especially children, recover completely with supportive care, though a minority progress to ESRD and may require combined immunosuppression and plasma exchange.

Induction therapy for RPGN across these entities generally involves pulse methylprednisolone followed by high‑dose oral prednisone, combined with cyclophosphamide and adjunctive plasma exchange in settings of pulmonary hemorrhage or anti‑GBM disease, which together can achieve remission or significant improvement in roughly 75–90% of patients when instituted before advanced renal failure. Maintenance regimens increasingly employ azathioprine or mycophenolate mofetil, which have demonstrated efficacy comparable to prolonged cyclophosphamide but with fewer adverse effects, while relapse episodes are typically treated with renewed high‑dose corticosteroids and cyclophosphamide.

Thrombotic microangiopathies and other systemic vascular disorders

Thrombotic microangiopathy (TMA) describes a group of occlusive small‑vessel disorders marked by endothelial injury, platelet‑rich thrombi containing abundant von Willebrand factor, thrombocytopenia, mechanical hemolysis, and diffuse onion‑skin intimal thickening, with the kidney frequently affected. Classic TMAs include thrombotic thrombocytopenic purpura (TTP) and hemolytic‑uremic syndrome (HUS), but phenotypically similar lesions occur in antiphospholipid syndrome, preeclampsia, systemic sclerosis renal crisis, malignant hypertension, and certain drug‑induced states. TTP results from severe deficiency of the metalloprotease ADAMTS‑13—due to inherited mutations or acquired autoantibodies—leading to accumulation of ultra‑large von Willebrand multimers and platelet aggregation; plasma exchange, combining plasmapheresis and replacement with fresh frozen plasma, yields survival in approximately 90% of treated patients.

HUS, usually following infection with Shiga toxin–producing Escherichia coli O157:H7 in young children, reflects Shiga toxin–mediated inhibition of ADAMTS‑13 secretion and promotion of platelet adhesion, and is managed with supportive care and dialysis, as specific therapies remain unproven. Preeclampsia, affecting 3–5% of pregnancies, is a multisystem endothelial disease associated with early rises in circulating sFlt‑1, reduced VEGF activity, placental underperfusion, and a renal lesion of glomerular endotheliosis; definitive treatment is delivery, while antihypertensives such as hydralazine, nifedipine, methyldopa, and labetalol are used to control blood pressure, with ACE inhibitors contraindicated. Antiphospholipid syndrome features hypercoagulability in the presence of antiphospholipid antibodies (e.g., anticardiolipin, lupus anticoagulant, anti‑β2‑glycoprotein I), and when catastrophic, it manifests as a TMA with renal involvement requiring intensive anticoagulation, plasma exchange, high‑dose steroids, and often immunoglobulin therapy.

Systemic sclerosis frequently involves the kidney, with 10–15% of patients developing scleroderma renal crisis characterized by abrupt severe hypertension, acute renal failure, and pathologic onion‑skin lesions of interlobular arteries; early and sustained ACE inhibitor therapy, particularly with captopril, has markedly improved outcomes and reduced progression to ESRD. Malignant hypertension, sickle cell disease, and atheroembolic disease are additional systemic vascular conditions that can severely compromise renal microvasculature, each with characteristic clinical settings—noncompliance and extreme blood pressure elevation, hemoglobinopathy‑related vaso‑occlusion, and cholesterol crystal embolization after vascular instrumentation, respectively—and require a combination of targeted medical management and supportive renal care.